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There is an unmet need for renoprotective drugs for more pronounced reduction of albuminuria beyond that provided by renin-angiotensin system (RAS) blockers and for effective slowdown of eGFR decline independent of albuminuria. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in reducing prespecified secondary composite kidney outcomes in cardiovascular outcome trials. However, GLP-1 RAs showed a prevailing anti-albuminuric effect, additional to that of RAS blockers, and a non-significant risk reduction in worsening of kidney function, at variance with sodium-glucose cotransporter 2 inhibitors. Mechanisms underlying renal protection with GLP-1 RAs are porly understood. Though treatment with GLP-1 RAs resulted in better glycaemic, blood pressure and body weight control versus placebo, correction for on-trial changes in these parameters did not significantly affect results. Anti-inflammatory/anti-oxidant effects via intracellular signalling through protein kinase A, natriuretic effect via inhibition of sodium-hydrogen exchanger 3 and reduction of hyperfiltration have been proposed as direct renoprotective effects., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We have analyzed a panel of T cell hybridomas specific for the chemically dominant epitope of hen egg-white lysozyme 48-61 which has asparagine 59 as an important T cell receptor contact residue. A number of T cells recognize 48-61 with asparagine at position 59, but not the aspartic acid or isoaspartic acid derivatives. Conversely, we find T cells that specifically recognize 48-61 bearing an isoaspartic acid at residue 59, but not asparagine. For other T cells, asparagine, aspartic acid, or isoaspartic acid at residue 59 is irrelevant. We present evidence that our previous distinction between type A and type B T cells is not explained by asparagine deamidation at residue 59.

Purpose: Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease induced by immunization with bovine melanin-associated antigen (MAA) and two adjuvants (complete Freund's adjuvant and purified pertussis toxin). This study was undertaken to explore whether an adjuvant is required in the induction of EAAU., Methods: Insoluble MAA was extracted from the bovine iris and ciliary body. Soluble bovine MAA was derived by treatment of insoluble MAA with the proteolytic enzyme, V8 protease. Lewis rats were immunized with the insoluble or soluble antigen, with or without adjuvant (complete Freund's adjuvant and purified pertussis toxin). Adoptive transfer of CD4+ and CD8+ T cells was performed to investigate the pathogenesis of EAAU., Results: Experimental autoimmune anterior uveitis can be induced in Lewis rats by immunization with 100 g insoluble bovine MAA alone without the use of adjuvants. The disease can be adoptively transferred to naive syngenic rats by primed CD4+ T cells. In contrast, soluble bovine MAA was not uveitogenic unless adjuvants were employed., Conclusions: The data suggest that EAAU can be induced in the Lewis rat without addition of an adjuvant. Future studies concerning the pathogenesis of EAAU can now be performed without the possible confounding effect of an adjuvant.

Purpose: Patients with active pars planitis have increased levels of a 36 kDa protein (p-36) in their circulation. The current studies were undertaken to determine the primary structure of this protein., Methods: A degenerate oligonucleotide probe based on the amino terminal sequence of p-36 was used to identify a clone from a human spleen cDNA library. The cDNA insert was subcloned into the EcoR1 site of pUC-19, and both strands were sequenced. Southern blot analysis was used to study the genomic hybridization pattern. p-36 cDNA was subcloned in a pSG5 expression vector, and the construct was used to transfect COS-7 cells., Results: The cDNA sequence contained an open reading frame of 966 base pairs encoding a protein of 322 amino acids, an untranslated region of 322 base pairs, and 2693 base pairs at the 5' and 3' ends, respectively. The deduced amino acid sequence showed 96.8% identity with the carboxy-terminal region of a yeast nucleopore complex protein, nup 100. Southern blot analysis of human genomic DNA revealed a simple hybridization pattern. Transfection of p-36 cDNA in COS-7 cells resulted in the presence of p-36 mRNA and expression of protein., Conclusions: The 36 kDa protein (p-36) detected at increased levels in the blood of patients with active pars planitis was cloned from a human spleen cDNA library. Its deduced amino acid sequence is homologous with the carboxy-terminal region of a nucleopore complex protein. Thus, we refer to this protein as nup36.

Purpose: This study was designed to investigate an animal model of uveitis that resembles anterior uveitis in humans after immunization with iris-ciliary body antigen., Methods: Male Lewis rats 6 to 8 weeks of age were immunized with the buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with complete Freund's adjuvant and pertussis toxin. Antigen was digested with various proteolytic enzymes and tested in different rodent strains for a uveitogenic response., Results: Acute iridocyclitis developed in both eyes of the Lewis rat during the second week after immunization, and the pattern of inflammation was similar to acute anterior uveitis in humans, with sudden onset, localization to the anterior uvea, and spontaneous resolution. Among the strains tested, F344 rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans rats were not. Experimental autoimmune anterior uveitis did not develop in any of the mice studied, nor was it induced by immunization with synthetic melanin, amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit iris-ciliary body. A soluble fraction derived from bovine melanin-associated antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted in a disease similar to that observed with intact BMAA., Conclusions: A model of anterior uveitis has been induced in the Lewis rat after immunization with bovine uveal antigen, and it resembles the acute iridocyclitis observed in humans. These results suggest that the pathogenic antigen is a melanin-associated protein(s) present within the iris-ciliary body.